Infant botulism is a disease of very restricted age distribution that results when Clostridium botulinum infects the intestinal tract and produces its toxin. Fulminant infant botulism may be one of the multiple causes of crib deaths currently grouped as the sudden infant death syndrome. Infant mice and rat models are colonized by C. botulinum when given orogastric challenges of the spores but they remain asymptomatic because the toxin is produced in he cecum-colon from where it is not absorbed. Attempts will be made to treat enterically, botulinum-colonized mice so that the toxin is absorbed and cause botulism. These include constipating the animals with drugs such as atropine, or using a cytotoxic agent, which acts on the gut, in amounts that will not of itself cause overt illness. If successful, the method may lead to an animal model that could be used to study sudden infant death of botulinum aetiology. Infant botulism is possible because the gut lacks the competitors of C. botulinum which are normally acquired as the infant grows older. The period of botulinum colonization of mice will be lengthened by putting challenged animals in an environment where they are less likely to acquire the competitors. Such lengthening of infection time could result in the hosts devloping botulism. Mice associated with a flora of 9 species are resistant to enteric botulinum colonization. The work will determine which species of the flora are important to the protection; the irreducible number could be two or more. When identified, their mechanism of action will be determined by testing their culture filtrates for ability to inhibit pure culture growth of C. botulinum, direct competition for the same niche in the cecum-colon, changing secreted bile acids into a form more toxic to the pathogen. Competitors different from those in the aforementioned flora will be isolated fro mthe cecum-colon of antibiotic treated mice that are regaining their resistance to colonization by C. botulinum. The results could suggest a way to make human infants resistant to botulinum toxicoinfection. The potential of Clostridium difficile and Clostridium tetani to cause an infant disease will be studied with the animal models used for infant botulism.